Moscow State University (MSU) Researchers Develop TAge A Universal Aging Clock

MOSCOW, Russia – An international group that includes scientists from Harvard Medical School, students from the Faculty of Bioengineering and Bioinformatics at Lomonosov Moscow State University (MSU), and staff at the A.N. Belozersky Institute of Physico-Chemical Biology at MSU has published a paper in Nature, and the journal placed it on the cover.

The team built universal transcriptomic clocks, called tAge. This bioinformatics tool studies the activity of thousands of genes and predicts chronological age, expected lifespan, and the risk of chronic disease. It also detects signs of rejuvenation during early embryonic development, cell reprogramming, and after old and young animals share a circulatory system.

How the New Clock Works

Aging research relies on “aging clocks,” which are mathematical models that estimate an organism’s chronological age from biomarkers such as DNA marks, physical activity data, blood tests, or even outward appearance. These tools can give a useful age estimate, but they often do a weak job of predicting how a diet change, drug, or genetic edit will affect lifespan.

The new transcriptomic clocks take a different route. Age looks at gene expression, which genes are active, which are silent, and how strongly they are working. The scale is large, too. The researchers trained the model on more than 11,000 samples from 25 tissue and organ types across four mammal species.

Some samples came from animals whose lifespans had been altered in experiments, which helped tAge pick up fine changes tied to health, disease, and possible geroprotectors.

Aging Modules and Early Embryonic Development

The team did more than find gene markers that work as broad signs of aging. They also grouped genes into modules that change together, and many of these modules were linked by function. That matters because it can help researchers find “master regulators,” the main switches that control parts of the aging process, the body’s response to aging, or resistance to it.

“Under the supervision of Alexander Tyshkovsky, the first author of our paper, I analyzed functional modules, groups of genes that work together and are tied to specific cellular or organismal functions,” says Darya Kholdina, a sixth-year student at the Faculty of Bioengineering and Bioinformatics at MSU, who defended her thesis just before publication.

“Different modules react differently to interventions. For example, caloric restriction slows the ‘metabolic’ clocks most strongly, while chronic diseases speed up the ‘inflammatory’ ones. This modular approach lets us measure these effects separately, which is important for targeted therapies.”

The study also found an unexpected pattern in early mouse development. From fertilization until about day 10 of pregnancy, the biological age measured by tAge drops fast. After that, it starts to rise again. In other words, a newly formed embryo does not begin at zero biological age. Instead, a controlled rejuvenation process resets age over several days.

“My task was to track what our transcriptomic clocks show at different stages of mouse embryonic development,” says Maria Davitadze, who also recently graduated from FBB MSU. “We saw a clear U-shaped pattern, age falls first, then rises. We also saw rejuvenation at the level of individual cell lineages, including neural, cardiac, and muscle cells.

This is a real reboot of biological age, and it supports the idea of a special ‘ground zero’ of organismal age during early embryogenesis. Vadim Gladyshev, a professor at Harvard Medical School and our collaborator, suggested the term ‘ground zero’ for this point.”

What Speeds Up tAge and What Slows it Down

The researchers tested tAge across several independent models. Gamma radiation, metabolic toxins, and long-term cell culture all pushed the biological age estimate upward. Immune and inflammatory modules aged the most in those cases.

On the other hand, activating the telomerase gene, the enzyme that extends chromosome ends, brought aging cells back to younger tAge values. Reprogramming cells into induced pluripotent stem cells, or iPSCs, had the same effect.

One of the strongest tests used heterochronic parabiosis, a procedure in which an old mouse and a young mouse are surgically joined so they share blood flow. After three months, tAge in the older mice dropped, and genes linked to regeneration and repair became active. That effect lasted long after the animals were separated.

What tAge Could Mean for Human Health

The clocks also worked in human data sets from large medical databases. They predicted the time of death and the risk of cardiovascular disease. Protein levels linked to key genes in the model were tied to diabetes, heart failure, hypertension, and depression.

“These results show that transcriptomic clocks are not just a toy for biologists, but a tool that can already help in the search for drugs that slow aging,” says Sergey Dmitriev, head of the Virus-Cell Interaction Department at the A.N. Belozersky Institute of Physico-Chemical Biology, MSU, and another co-author of the paper.

“Most importantly, many of the rejuvenation signatures we found, for example, those linked to early embryogenesis or cellular reprogramming into iPSCs, may be possible to recreate in adult cells by briefly turning on the same ‘master regulators’ that start biological age reduction.

“In principle, current methods already allow these changes to be done in a controlled and safe way, for example, with mRNA technologies, which we actively develop in our department.

Further research will show whether it is possible to switch on gene-expression programs in adult cells that are similar to those in embryos and iPSCs, while preventing uncontrolled cell growth and loss of cell identity.”